This invention relates to a system for performing an assay of biological cell samples, and more particularly, for providing an automated method and arrangement of measuring attributes of the image fields and cells of slide mounted tissue samples.
The diagnosis and/or prognosis of a patient's condition frequently includes the removal of a cell sample, such as a tissue mass, from the patient. Although an attending physician may have good intuition regarding the patient's diagnosis and/or prognosis, confirmation of the diagnosis with histological examination of the cell sample removed from the patient is necessary. The histological examination entails cell staining procedures which allow the morphological features of the cells to be seen relatively easily in a light microscope. A pathologist, after having examined the stained cell sample, makes a qualitative determination of the state of the tissue and reaches a conclusion regarding the prognosis for the patient. While this diagnostic method has a long history, it is somewhat lacking in scientific rigor since it is heavily reliant on the subjective judgment of the pathologist and it is extremely time-consuming.
The alternative to the strictly qualitative and time-consuming human analysis is automated cell analysis where the pathologist uses specialized equipment to perform the analysis. Flow cytometry equipment is one type of automated apparatus for cell analysis. With flow cytometry, mass tests are performed in gross on a specimen cell population without a researcher being able to exclude or include certain data of the population. The specimen is measured "as is" without really knowing what cells are being measured and how many. Important single cell data or data from relatively small groups of cells are lost in the overall averaging of a specimen. Further, relatively large amounts of a specimen have to be used to provide a required level of accuracy. Again, small changes in individual cells or small cell populations cannot be discerned.
Commercially available general purpose flow cytometers are very expensive and can handle only liquid blood specimens or tissue disaggregated specimens. Additionally, flow cytometers are incapable of working on standard tissue sections or using conventional microscope slides which are the preferred specimen forms of pathology laboratories.
Although the automation of cell analysis using microscope slide cell samples is exceedingly difficult, such has been automated to a human-machine interactive level. One such method and apparatus is described in U.S. Pat. No. 4,471,043 to Bacus, for Method And Apparatus For Image Analysis Of Biological Specimens. Cell samples are attached to slides and an operator adjusts the system optics to view desired image fields of the cell sample. The operator then selects and classifies particular cell objects of the sample. After such operator action, the automated equipment quantitatively measures particular attributes of the selected and classified cell objects and records a digital representation of the optical image. The measured attributes can be reported on a per object basis or on an accumulated basis, and the stored image representations can later be read from memory for review.
The automation of analysis of slide cell samples as described in U.S. Pat. No. 4,471,043 has provided many advantages over both the historical pure human analysis and the automated flow cytometry analysis. Large amounts of human operator time and judgment are still required to complete a tissue section assay. A need exists, however, for improvements in the automation of analysis of slide cell samples, and particularly, for slide tissue samples.